Why do people respond so differently to the same drugs?

Maureen Dowd, a 62-year-old Pulitzer Prize–winning columnist for the New York Times, had a bad marijuana trip
earlier this year. As part of her research into the legalization of
recreational cannabis in Colorado, she ate a few too many bites of a
pot-infused candy bar, entered a “hallucinatory state,” and spent eight
paranoid hours curled up on her hotel room bed. Dowd used the experience
as a jumping-off point to discuss the risks of overdosing on edible
marijuana, which has become a major issue in pot-friendly states.
It’s also possible, however, that Dowd just doesn’t handle cannabis
very well. While pot mellows most people out, everyone has heard of
someone who barricaded himself or herself in a dorm room after a few
bongs hits in college. (Or maybe that someone is you.) Why do people
react so differently to the same drug?

The question itself may be something of a fallacy. Cannabis is not a
single drug—it contains dozens of compounds, and they appear to have
varying, and sometimes opposing, effects on the brain.
Tetrahydrocannabinol, or THC, and cannabidiol, or CBD, have been the
subject of some intriguing research. In 2010, researchers showed that pretreating people with a dose of CBD can protect against the less pleasant effects of THC, such as paranoia. In a similar 2012 study,
participants took pills that contained only one of the two chemicals,
rather than the combination that you receive in cannabis. The subjects
who took THC pills were more likely to suffer paranoia and delusion than
those who took CBD.

The researchers went one step further to investigate which specific
cognitive effects of THC are likely to lead to paranoia and other
symptoms of psychosis. After taking either THC or CBD, participants
watched a series of arrows appear on a screen and responded by
indicating which direction the arrows were pointing. Most of the arrows
pointed directly left or right, but occasionally a tilted arrow
appeared. (Researchers called the tilted arrows “oddballs.”) Subjects
who took the CBD had a heightened brain activity responseto the
oddballs. That’s the way a nondrugged person typically
reacts—repetitions of the same stimulus don’t interest us, but a sudden
change grabs our attention. The THC-takers had an abnormal response:
They found the left and right arrows, which constituted the overwhelming
majority of the images, more noteworthy than the oddballs. The
researchers’ interpretation is that THC may undermine our ability to
ignore routine, unimportant stimuli. Ignoring the ordinary is an
important skill—we can’t function if every chirping bird or billboard
grabs our attention and refuses to let go. Focusing obsessively on every
meaningless detail in the environment may contribute to the paranoia
that some pot users experience.

The differing effects of THC and CBD partially explain why some
marijuana strains—which differ in the ratios and amounts of THC and
CBD—are believed to provide giddy, excited highs, while others are
thought to mellow the user, regardless of one’s personal neurological
peculiarities.

Although both THC and CBD are present in marijuana, your brain may be
more receptive to one of the chemicals than the other. Maureen Dowd’s
brain may have a strong affinity for THC, while the mellower smokers may
take up CBD more efficiently.

There is probably also a psychological element in addition to the
neurochemical explanation. Consider the effects of alcohol. There are
mean drunks, loud drunks, amorous drunks, withdrawn drunks, teary
drunks, and many more kinds. There are no differences in the drug
itself—unlike cannabis, alcohol has only one psychoactive substance—so
there has to be another explanation.

There are scads of studies exploring the diverse effects of alcohol,
much of it focusing on variations in alcohol-related aggression, but
none of the studies are entirely satisfying. Psychological research
rarely is. (That’s not a knock on psychologists or psychiatrists—it’s
just a very tricky field.)

One theory is that some people don’t care very much about the
consequences of their actions, even when they’re sober. When these
people drink, they get aggressive, and their lack of foresight means
they don’t bother to check their mean-drunk impulses. In a 2012 study,
researchers at Ohio State showed that people who ignored consequences
when sober got really excited about shocking their opponents
in a drunken reflex competition. The study was widely publicized, but
shocking a person in a laboratory setting is vastly different from
punching someone in a bar. The legacy of the infamous Milgram experiment
is also relevant—anyone participating in a psych experiment allegedly
involving shocking other participants may well know it’s just pretend.
Several other personality characteristics, such as anxiety levels,
have been suggested as explanations for how people behave when
intoxicated. Most of these studies are based on laboratory scenarios
that don’t mimic well the drinking experiences you get in the wild.

There may a genetic basis for differing responses to alcohol. In a 2010 twin study,
researchers attributed one-third of the variation in alcohol-induced
aggression levels to genetic factors. The research was based on
self-reporting, though, and the ability to estimate our own anger and
aggression levels isn’t necessarily consistent from person to person.

Although the research hasn’t settled on simple explanations, it’s clear that some
combination of personality traits, genetics, and experience affects how
people respond to intoxicants. You can’t blame it all on the drug.
Maureen Dowd’s rough night in Denver had something to do with the amount
and kind of dope she consumed, as well as her own reaction to certain
psychoactive chemicals. But her psychological makeup also likely played a
role. I can think of a few people who might accuse her of an inability to consider the consequences of her actions.

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